Exposure to stress can have long-term physiological and psychological consequences. The current proposal will examine the effects of prior exposure to social stress on the histological, physiological and behavioral consequences of cardiac arrest and cardiopulmonary resuscitation (CPR). In addition, stress-induced alterations in corticosteroid responses will be examined as one of the mechanisms through which social cues can influence outcome in our mouse model of cardiac arrest. The data collected as part of this proposal will increase our understanding of the basic pathophysiological mechanism of global ischemia and the roles that social interaction and the hypothalamic-pituitary-adrenal axis play in influencing post-cardiac arrest neuronal death, neuronal restructuring, anxiogenic-like behavior and cognitive function. Ultimately, understanding the factors that modulate neurotoxicity and behavioral outcomes may facilitate the development of therapeutic approaches for the prevention and treatment of cerebral ischemia. Taken together, the proposed studies will provide a neurobiological foundation on which to study the effects of stress on cardiac arrest/CPR outcome, and may provide insights into the mechanisms underlying individual differences in outcome following an ischemic event.